Abnormalities of the intrauterine environment may be acute or chronic in nature and are associated with increased perinatal morbidity and mortality. For example, fetuses with growth retardation are less able to tolerate decreases in uterine blood flow (UBF) as evidenced by abnormal Apgar Scores, the occurrence of meconium-stained amniotic fluid, and increased perinatal mortality. Understanding the fetal responses to these adverse intrauterine events is predicated upon understanding the complex integrated physiologic responses that might occur. Thus, the broad objective of this project is to delineate and integrate neurohumoral, cardiovascular, and metabolic events associated with fetal "distress." The specific aims are to determine: whether arginine vasopressin (AVP) is important in the release of other neurohumoral agents elevated in response to fetal "distress", e.g., ACTH and cortisol, and delineate their interaction; if an interaction exists between fetal AVP release, glucagon secretion, and glucose homeostasis; if interactions exist between catecholamines (C) and AVP during fetal "distress"; and finally, what is the pattern of prolactin (PRL) secretion during fetal "stress" and its interaction with AVP and ACTH. To accomplish these aims, studies have been designed utilizing chronically-instrumented pregnant ewes and fetal sheep studied remote from surgery and in the last third of pregnancy, 110 days to term (term=144+5 days). The patterns of hormonal secretion and interaction will be determined from serial observations obtained before, during, and after an experimental intervention, measuring hormones by radioimmunoassay (AVP, C, ACTH, PRL, and cortisol), while continuously monitoring UBF, heart rate, blood pressure, amniotic fluid pressure, O2 content, and arterial PO2, PCO2, and pH in the mother and fetus. In selected studies blood glucose and lactate will be determined and alterations in fetal regional blood flows evaluated using radiolabelled microspheres. The role of AVP in the pathogenesis of fetal meconium release will be examined by monitoring gastrointestinal intraluminal pressure, i.e., peristalsis. Degrees of fetal "distress" will be obtained by acutely decreasing UBF with infusions of C and/or arterial vascular occluders. Finally, the actions of AVP (neurohumoral, cardiovascular, or metabolic) will be blocked using passive immunization with AVP-antiserum. From the results of these studies a better understanding of fetal adaptation to intrauterine "stress" and hormonal interaction will be obtained.